A New Cardiac Regulator?

Phosphatidylethanolamine-binding protein (PEBP, also called Raf-1 kinase inhibitor protein), which is a precursor to hippocampal cholinergic neurostimulating peptide (HCNP), is found in various tissues, including brain, adrenals, and platelets. Noting that PEBP and HCNP have been found in synaptic vesicles and that HCNP is secreted by hippocampal neurons, Goumon et al. investigated the possible localization of these peptides in adrenal chromaffin cells (which are related developmentally and functionally to sympathetic neurons and, when stimulated, release catecholamines into the blood). The authors used a combination of techniques to show that PEBP could be found in the cytoplasm and the secretory granules of cultured bovine adrenal chromaffin cells. Stimulation of the cells with increased extracellular concentrations of K+ or with nicotine led to PEBP release into the extracellular solution with a similar time course and nicotine concentration dependence as for release of chromagranin A (a known constituent of chromaffin granules). PEBP was also secreted by platelets treated with thrombin receptor-activating peptide and could be detected in bovine serum. The authors used two-dimensional liquid chromatography-tandem mass spectrometry to show that HCNP was also present in chromaffin granules. Suspecting a possible endocrine role--and based on the known effects of catecholamines and the chromagranin A-derivative vasostatin I--the authors examined the effects of HCNP on isolated frog heart and discovered that it decreased stroke volume and stroke work and counteracted the positive inotropic effects of the β-adrenergic agonist isoproterenol. Thus, HCNP may represent a new endocrine modulator of cardiac physiology.